The proposed program is designed to examine the mechanisms by which cellular electrolyte exchange and renal transport mechanisms maintain homeostatic control of electrolyte, water & acid-base balance of the body. A number of different experimental approaches will be utilized. In vitro microperfusion experiments will examine the characteristics of epithelial function of the various nephron segments using electrophysiological, ion sensitive electrode, & bidirectional flux measurement techniques. One series of studies is designed to elucidate the mechanisms of acidification in the proximal, distal & collecting tubules by utilizing the newly developed pCO2, in situ pH and equilibrium pH electrodes. Another series of studies examines the regulation of salt & water transport across various nephron segments. Of special interest will be the effect of various hormones on the transport processes. The in vivo micropuncture studies are also designed to examine the regulation of electrolyte & acid-base transport across the accessible nephrons. Many parallel protocols will be conducted by in vivo micropuncture and in vitro microperfusion techniques. Microelectrode development will be continued with emphasis on the development of bicarbonate and sodium sensitive electrodes. The purpose of these new electrodes is to utilize them to examine the basic salt/water and acid-base balance issues by the microperfusion & micropuncture methods. In summary, the proposed studies use a number of newly developed techniques to examine forces which regulate salt and water transport in normal, perturbed & diseased states.